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Ultrastructural injury to interstitial cells of Cajal and communication with mast cells in Crohn's disease
Intestinal Disease Research Program, McMaster University, Hamilton, Ont., Canada.
Intestinal Disease Research Program, McMaster University, Hamilton, Ont., Canada, Centre for Academic Surgery, Alexandra Wing, Royal London Hospital, Whitechapel, London E1 1BB, United Kingdom.
Linköping University, Department of Clinical and Experimental Medicine, Surgery . Linköping University, Faculty of Health Sciences. Östergötlands Läns Landsting, Anaesthesiology and Surgical Centre, Department of Surgery UHL.
Department of Pathology and Molecular Medicine, McMaster University, Hamilton, Ont., Canada.
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2007 (English)In: Neurogastroenterology and Motility, ISSN 1350-1925, E-ISSN 1365-2982, Vol. 19, no 5, 349-364 p.Article in journal (Refereed) Published
Abstract [en]

Crohn's disease associated dysmotility has been attributed to fibrosis and damage to enteric nerves but injury to interstitial cells of Cajal (ICC) could also be involved. We assessed ICC in specimens obtained from patients with Crohn's disease and determined the relation between ICC and the inflammatory infiltrate, particularly mast cells (MC) using quantitative immunohistochemistry and electron microscopy. Ultrastructural injury to ICC was patchy in all ICC subtypes but ICC-Auerbach's plexus (AP) showed damage more frequently, i.e. swelling of mitochondria, decreased electron density, autophagosomes and partial depletion of the cytoplasm. Light microscopy confirmed a significant decrease in c-kit immunoreactivity for ICC-AP and an increased number of MC in the muscularis externa. Electron microscopy showed MC exhibiting piecemeal degranulation and making frequent and selective membrane-to-membrane contact with all types of injured ICC which suggests chronic release of granule content to affect ICC. Extent of ICC injury was not associated with duration of the disease. In conclusion, ultrastructural injury and loss of ICC-AP is evident in Crohn's disease. Epidemiological and morphological data suggest that ICC have the capacity to regenerate in spite of the chronic insult. The muscularis hosts a marked number of MC that exhibit piecemeal degranulation associated with ICC and may facilitate ICC maintenance. © 2007 The Authors.

Place, publisher, year, edition, pages
2007. Vol. 19, no 5, 349-364 p.
Keyword [en]
Inflammatory bowel disease, Interstitial cells of Cajal, Mast cells
National Category
Natural Sciences
URN: urn:nbn:se:liu:diva-49810DOI: 10.1111/j.1365-2982.2006.00894.xOAI: diva2:270706
Available from: 2009-10-11 Created: 2009-10-11 Last updated: 2010-05-24

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Söderholm, Johan D
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Surgery Faculty of Health SciencesDepartment of Surgery UHL
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